Larger Infarct Size Research Articles

Unilateral carotid artery ligation in the Mongolian gerbil as a model for testing infarction-reducing therapies

This study evaluates infarct size measurement as an indicator of cerebral ischaemia outcome in a placebo-controlled trial of potential cerebral protection in the unilateral carotid artery ligation in the Mongolian gerbil. Ibuprofen was used in an effort to manipulate infarct size as this agent has been shown to reduce ischaemia in myocardial infarction. Using measurements obtained through an infarct-sizing technique and a statistical power analysis of the method, the sample sizes needed to obtain significant results were projected for this model. In this case, it was not possible to demonstrate an effect of ibuprofen on infarct size although a tendency towards larger infarct size in ibuprofen-treated compared with placebo-treated gerbils was observed (36.1 +/- 10.1% versus 30.0 +/- 17.5%). The sample sizes needed to find significant changes in infarct size indicate that this model finds a practical use in studying therapies which will alter infarct size by at least 50%. For example, to detect a 30% change in infarct size, 33 successfully infarcted gerbils per group would be needed, but a 50% change would require a more tenable 13 infarcted gerbils per group. However, given the 40% infarction rate of occluded gerbils seen in this study, almost 33 gerbils per group would be required to detect a 50% change. In addition, somatosensory evoked potential was compared with neurological examination as a predictor of infarction. It would be helpful to be able to pre-screen for infarcted gerbils immediately after occlusion in order to direct infarcted gerbils into control and treated groups. Somatosensory evoked potential successfully predicted infarction with a 90% accuracy in 21 gerbils compared with neurological evaluation which was 100% accurate. But the somatosensory evoked potential prediction was made within 15 min of occlusion as opposed to the 6 h of observation during which the neurological evaluation was made.

Reduction of myocardial injury with verapamil before aortic cross-clamping

The effect of verapamil administered before aortic crossclamping was assessed in 40 patients undergoing elective coronary artery bypass grafting. Myocardial protection consisted of cold blood potassium cardioplegia, topical ice slush, and moderate (28 °C) systemic hypothermia. Patients were randomly divided into two groups: group 1 (18 patients) received verapamil (0.1 mg/kg up to 10 mg) intravenously three to five minutes before aortic crossclamping; group 2 (22 patients) did not (control). Myocardial injury was assessed by cumulative release of the cardiac-specific noenzyme of creatine kinase (CK-MB) after release of the aortic cross-clamp. Release of CK-MB was significantly lower in the verapamil group (44.9 ± 6.2 versus 72.2 ± 9.0 IU at 24.5 hours, p = 0.005). Calculated total infarct size was also lower in the verapamil group (6.0 ± 0.9 versus 8.9 ± 1.0 g-Eq, p = 0.035). Individual CK-MB release curves showed either one or two peaks. The two-peak pattern was more frequent in control patients (18 of 21 control patients versus 6 of 18 verapamil patients, p = 0.001) and was associated with a larger infarct size. Atrioventricular pacing was not required in any verapamil patient, but was needed in 1 control patient. We conclude that verapamil administered before aortic cross-clamping protects against myocardial injury during coronary artery bypass grafting with no increase in the incidence of atrioventricular block.

Heart Block as a Predictor of In-hospital Death in Both Acute Inferior and Acute Anterior Myocardial Infarction

We investigated the relationship between atrioventricular block and in-hospital mortality in 705 successive patients admitted with a first Q-wave myocardial infarction of the anterior or inferior wall. Second- or third-degree atrioventricular block developed in 61 (8.6 per cent) patients and was more frequent in inferior (12.4 per cent) than anterior infarctions (4.9 per cent). A multiple logistic regression identified three factors which were independently correlated with block: inferior infarction, older age and larger infarct size as determined by cardiac enzymes. Mortality was 27.9 per cent in patients with block and 9.3 per cent in those without; it was significantly higher in both anterior (47.0 per cent vs 11.8 per cent) and inferior (20.4 per cent vs 6.7 per cent) infarction groups. When age, infarct size, infarct site and block were analysed simultaneously as predictors of death, block was a significant independent prognostic factor. The relative risk of death, corrected for age and infarct size, in patients showing block was similar for anterior and inferior infarction. Analysis of deaths revealed a higher incidence of unheralded death in inferior infarcts associated with high-degree block.

冠動脈疾患患者における末梢動脈硬化の進展に関する研究 特に四肢・頚動脈動脈硬化病変合併の臨床像と冠疾患臨床背景との関連性について

Coexisted peripheral vascular disease (PVD: ankle/brachial pressure index A/PBI less than 0.75) or carotid artery disease (CTD: Brochenbrough's supraorbital Doppler flow analysis) were diagnosed by non-invasive testings, and correlated with clinical pictures and coronary backgrounds in 121 consecutive patients with confirmed coronary artery disease. PVD were found in 16.5%, CTD in 33.1% and both PVD and CTD in 9.9%. The mean age of PVD(+) patients was significantly higher than that of PVD(-) patients, furthermore CTD(+) patients displayed a significantly larger number of coronary risk factors than CTD(-) patients. Concerning the subjective symptoms, 20% of PVD(+) patients and 45% of CTD(+) patients were asymptomatic regarding PVD or CTD symptoms. However the degree of calcification of the aortic arch on the chest X-film (n = 104) significantly correlated with A/BPI. In patients with AMI, PVD patients showed significantly higher peak CK and CK-MB values than those in PVD(-) patients, which suggested large infarct size in coexistent PVD patients. With respect to the relationship between coronary risk factors, there was a statistically significant difference between PVD(+) patients and PVD(-) patients in terms of the obesity ratio in males as well as hypercholesterolemia ratio and obesity ratio in females. In CTD patients, significant differences between CTD(+) and CTD(-) patients were found with respect to the smoking ratio and obesity ratio in males as well as the smoking ratio in females. In whole study patients, A/BPI with lowered and A.I. (atherogenic index) increased significantly when patients possessed coronary risk factors equal or more than 4 items, which suggested the progression of PVD with increasing number of coronary risk factors.

Electrophysiological and anatomic differences between canine hearts with inducible ventricular tachycardia and fibrillation associated with chronic myocardial infarction.

This study examined electrophysiological and anatomic differences between dogs with ventricular tachycardia (VT) and fibrillation (VF) inducible by programmed ventricular stimulation 7-21 days after left anterior descending coronary artery ligation. Of 106 dogs studied, 40 had inducible VT, 19 had inducible VF, and 47 had no inducible arrhythmias. Differences between these three groups of animals were examined with cardiac mapping (to determine ventricular activation time in sinus rhythm) and post-mortem pathology (to measure infarct size and to reconstruct the anatomy at the infarct edge). Animals with inducible VT had longer maximal epicardial activation time (127 +/- 8 msec) than did animals with inducible VF (91 +/- 8 msec, p less than 0.05) or animals with no inducible arrhythmias (75 +/- 2 msec, p less than 0.001). Delayed epicardial activation occurred in 90% of animals with VT, 42% of animals with VF, and in only 6% of animals with no inducible arrhythmias. Endocardial and myocardial activation times were similar for the VT and VF groups. Infarct size was 18 +/- 2% of the ventricles for the VT group, much higher than for the VF group (11 +/- 2%, p less than 0.001) or for the group with no inducible arrhythmias (9 +/- 1%, p less than 0.001). The maximum diameter of viable muscle bundles interdigitating with scar tissue at the infarct edge was much larger in animals with VT (2.4 +/- 0.2 mm) than in animals with VF (1.8 +/- 0.2 mm, p less than 0.05) or animals with no inducible arrhythmias (1.7 +/- 0.1 mm, p less than 0.01). Thus, when compared with animals with inducible VF, animals with inducible VT had longer epicardial activation time, larger infarct size and viable muscle bundles of larger diameter at the infarct edge.

Pericarditis in acute myocardial infarction: Characterization and clinical significance

To determine the significance of pericarditis following acute myocardial infarction, the hospital course and 12-month follow-up were analyzed in 703 patients enrolled in the Multicenter investigation of the Limitation of infarct Size (MILIS). Pericarditis, defined by the detection of a pericardial rub, occurred in 20% of the patients (n = 141) and was more likely to follow Q wave than non-Q wave infarction (25% vs 9%, p < 0.001). Patients with pericarditis experienced more serious myocardial damage compared to those without pericarditis, as evidenced by a larger infarct size (25 ± 1 vs 17 ± 1 MB-CK gm-Eq/m 2, p < 0.001), a lower admission left ventricular ejection fraction (42 ± 1% vs 48 ± 1%, p < 0.001), and a higher incidence of congestive heart failure (47% vs 26%, p < 0.001) and atrial tachyarrhythmias (16% vs 10%, p < 0.05). When patients were classified by the presence of Q or non-Q wave infarction, these differences persisted although statistical significance was not always achieved due to smaller sample size. Mortality at 12-month follow-up for patients with pericarditis was 18% compared with 12% for patients without pericarditis ( p = 0.055). This mortality difference could be accounted for in part by the lower ventricular ejection fraction in patients with pericarditis ( p = 0.20 after adjustment).

Physiologic bases for anterior ST segment depression in patients with acute inferior wall myocardial infarction

Patients with acute inferior myocardial infarction commonly have ST segment depression in the anterior precordial leads. This may reflect either reciprocal changes from the inferior ST elevation or primary ST depression from additional anterior subendocardial ischemia. From a biophysical perspective reciprocal changes should be uniformly anticipated from basic dipole theory. Detection will vary with the size, location, orientation, and electrical intensity of the lesion and with the ECG lead system deployed to register the anterior changes. Alternatively, acute occlusion of the right coronary arterv may produce ischemia in the anterior left ventricular wall supplied by a stenotic anterior descending coronary artery. Anterior ischemia may result from the abnormal hemodynamics or the reduced collateral flow produced by acute right coronary artery occlusion. Thus both mechanisms are based on sound physiologic principles. A review of the clinical literature suggests that such patients represent a heterogeneous group. In some instances coexistent anterior ischemia is present, whereas in others the anterior ST depression is the passive reflection of inferior ST elevation augmented in many cases by a large infarct size or more extensive posterobasal or septal involvement.

Prognostic significance of location and type of myocardial infarction: Independent adverse outcome associated with anterior location

To determine the relative prognostic significance of location (anterior or inferior) and type (Q wave or non-Q wave) of infarction, the hospital course and follow-up outcome (mean duration 30.8 months) of 471 patients with a first infarction were analyzed. Analyses were performed grouping the patients according to infarct location (anterior, n = 253; inferior, n = 218), infarct type (Q wave, n = 323; non-Q wave, n = 148), and both location andtype (inferior non-Q wave, n = 85; inferior Q wave, n = 133; anterior non-Q wave, n = 63; and anterior Q wave, n = 190).Patients with anterior infarction had a substantially worse in-hospital and follow-up clinical course compared with those with interior infarction, evidenced by a larger infarct size (21.2 versus 14.9 g Eq/m2creatine kinase, MB fraction [MB CK], p < 0.001), lower admission left ventricular ejection fraction (38.1 versus 55.3%, p < 0.001) and higher incidence of heart failure (40.7 versus 14.7%, p < 0.001), serious ventricular ectopic activity (70.2 versus 58.9%, p < 0.05), in-hospital death (11.9 versus 2.8%, p < 0.001) and total cumulative cardiac mortality (27 versus 11%, p < 0.001). Patients with Q wave infarction similarly experienced a worse in-hospital course compared with patients with non-Q wave infarction, evidenced by a larger infarct size (20.7 versus 12.7 MB CK g Eq/m2, p < 0.001), lower admission left ventricular ejection fraction (43.7 versus 50.6%, p < 0.001), and a hight, incidence of heart failure (31.9 versus 21.6%, p < 0.05) and in-hospital death (9.3 versus 4.1% p < 0.05). However, there was no increased rate of reinfarction or mortality in hospital survivors with non-Q wave infarction compared with those with Q wave infarction, and total cardiac mortality was similar (16 versus 21%, p = NS).To evaluate the role of infarct location and type independent of infarct size, patients were grouped according to quartile of infarct size, and outcome was reanalyzed within each group. Patients with anterior infarction demonstrated a lower left ventricular ejection fraction on admission and after 10 days than did patients with inferior infarction, even after adjustment for infarct size, as well as a higher incidence of congestive heart failure and cumulative cardiac mortality. When patients were evaluated on the basis of both location andtype of infarction, those with anterior infarction exhibited a worse hospital course and cumulative cardiac mortality than did those with inferior infarction, whether the infarction was non-Q wave or Q wave in type. Life-table analysis of cardiac mortality using the Cox proportional hazards regression model demonstrated that location, but not type, of infarction exerted an independent prognostic effect.Thus, patients with anterior infarction experience a more complicated hospital and follow-up course than do patients with inferior infarction despite adjustment for infarct size and regardless of type of infarction (Q wave or non-Q wave). The disparity between outcomes in patients with anterior as opposed to inferior infarction may be due to coexistent right ventricular infarction in patients with inferior infarction, resulting in less left ventricular impairment relative to the total MB CK released, as well as to differences in topographic responses to infarction between the two sites.

Cardioembolic stroke, early anticoagulation, and brain hemorrhage. Cerebral Embolism Study Group

Brain hemorrhage is a feared complication of early anticoagulation therapy in patients with cardioembolic brain infarction. We describe nine patients with cardioembolic stroke who experienced clinical deterioration associated with computed tomography-documented hemorrhagic transformation. The clinical features of these nine patients combined with 15 previously reported cases were analyzed to determine factors associated with hemorrhagic worsening. Patient age, embolic source, and intensity of anticoagulation were not associated with hemorrhagic worsening. Large infarct size and initiation of anticoagulation after early (less than 12 hours) computed tomography were associated with hemorrhagic transformation and clinical worsening in patients who received anticoagulation therapy.

Reperfusion Arrhythmias during Coronary Reperfusion Therapy in Man: Clinical and Angiographic Correlations

We hypothesized that patients suffering acute myocardial infarction who have reperfusion arrhythmias (RPA) during intracoronary streptokinase infusion (ICSK) would have different clinical and angiographic characteristics and a larger infarction size than those who achieved reperfusion without RPA. Of 35 patients who received intracoronary streptokinase, 27 had successful reperfusion documented by angiography. Successful reperfusion was accompanied by RPA in eight patients and no RPA in 19 patients. RPA included episodes of ventricular tachycardia in one, idioventricular rhythm in four, junctional bradycardia in one, or AV block in two patients which occurred at the time of reperfusion. Myocardial infarction size was calculated using creatine kinase-MB (CK-MB) isoenzyme time activity curves using standard methods. The mean CK-MB g equivalents (eq) for those with RPA was 71 +/- 25 (+/- 1 SD) and for those with no RPA was 45 +/- 24 (p less than .04). In patients with RPA, ejection fraction rose 5 +/- 14 percentage points before discharge, but fell 10 +/- 13 points in those with RPA (p less than .03). There was no difference between groups in total dose of streptokinase, final degree of stenosis of the affected vessel, reocclusion rate, or time from onset of symptoms to reperfusion. We conclude that patients suffering acute myocardial infarction who have RPA during ICSK in most cases have a larger infarction site or a more "stunned myocardium," as indicated by greater CK-MB release and fall in ejection fraction which is not due to increased time of ischemia.

Serial analysis of electrically induced ventricular arrhythmias in a canine model of myocardial infarction

To determine the rate of induction, specificity and evolution of electrically induced postmyocardial infarction ventricular arrhythmias, 10 dogs that underwent a sham operation and 20 dogs with experimental transmural apical myocardial infarction underwent serial closed chest electrophysiologic studies with programmed ventricular stimulation under light anesthesia 1, 2, 4 and 6 weeks after the operation. The reproducibility of the electrically induced ventricular arrhythmias was at a maximum when three extrastimuli were used during ventricular pacing for induction. The reproducibility of the arrhythmias was also a function of the age of the infarct. Electrically induced sustained monomorphic ventricular tachycardia, observed in 45 to 50% of the animals, was a highly specific postinfarction finding (0% specificity in control animals, regardless of the mode or timing of programmed cardiac stimulation), whereas nonsustained polymorphic ventricular tachycardia was not. The specificity of induced ventricular fibrillation was a function of the mode and timing of programmed stimulation. The rate of induction of the electrically induced ventricular arrhythmias did not change significantly during the 6 week period after myocardial infarction. A large infarct size (determined by postmortem examination) and a low left ventricular ejection fraction (determined during premortem cardiac catheterization) were the only variables identified that predisposed the animals to electrically induced sustained monomorphic ventricular tachycardia. These factors, however, did not correlate with the presence of electrically induced ventricular fibrillation or nonsustained ventricular tachycardia.

Left and right ventricular function in inferior acute myocardial infarction and significance of advanced atrioventricular block

Of 139 consecutive patients with a first inferior acute myocardial infarction, 26 (19%) had advanced atrioventricular (AV) block and 113 (81%) did not. All were evaluated by 2-dimensional echocardiography (2-D echo) and radionuclide angiography. Patients with advanced AV block had lower radionuclide left ventricular (LV) ejection fraction (51 +/- 10 vs 58 +/- 11%, p less than 0.01), higher LV wall motion score on 2-D echo (5.6 +/- 2.6 vs 3.1 +/- 2.7, p less than 0.001), lower radionuclide right ventricular (RV) ejection fraction (32 +/- 15 vs 39 +/- 16%, p less than 0.001) and higher RV wall motion score on 2-D echo (3.4 +/- 1.7 vs 1.5 +/- 2, p less than 0.002) than did patients without AV block. The incidence rate of RV dysfunction was higher in patients with advanced AV block (78 vs 40%, p less than 0.02), and the mortality rate was also higher (although not significantly) in patients with advanced AV block (15 vs 6%). In conclusion, patients with inferior acute myocardial infarction and advanced AV block have larger infarct sizes (as seen on radionuclide angiography and 2-D echo) and lower RV and LV function than patients without AV block. This finding may explain the higher mortality rate observed in this group.

Quantitative relationships between thallium-201 estimated myocardial infarct size and left ventricular function in the acute or convalescent phase of the first attack of myocardial infarction.

Correlations between left ventricular (LV) function and infarct size estimated by computer-assisted thallium (Tl)-201 scintigraphy were studied in 16 patients in the acute or convalescent phase of the first attack of transmural myocardial infarction (MI). Tl-201 estimation of the infarct size was done using a "corrected" circumferential profile method, by which the total defect score could be obtained. The LV function was evaluated by radionuclide angiography, echocardiography and cardiac catheterization study. The following results were obtained : 1) A close inverse relationship was found between the defect score and the ejection fraction (r=-0.649, r<0.01). 2) The linear correlation diastolic pressure and -0.616 (p < 0.02) between the defect score and the cardiac index. 3) There was a linear correlation between the defect score and the LV end-diastolic dimension (r= -0.852, p < 0.001). However, there was no relation between the defect score and the left atrial dimension. When the LV indices were compared between the small (S) and the large (L) defect score group, the L defect group had faster heart rate, larger LV chamber size and the smaller stroke volume index than the S defect group. However, there was no significant difference in the cardiac index between these 2 groups. These results suggest that the LV dilatation in acute or convalescent phase of the first attack of transmural MI is an ominous sign because it was usually accompanied by large infarct size. The present study also indicates that LV dilatation accompanying a large infarct does not satisfactorily compensate for LV dysfunction by Frank-Starling mechanism, because the stroke volume index decreased in proportion to the infarct size and the cardiac index was maintained by an increase in heart rate in cases with LV dilatation.

EFFECTS OF EARLY ADMINISTRATION OF A HIGHLY PURIFIED HYALURONIDASE PREPARATION (GL ENZYME) ON MYOCARDIAL INFARCT SIZE

79 patients with suspected myocardial infarction entered a randomised trial to establish the safety of early intravenous administration of a highly purified hyaluronidase preparation (GL enzyme) and to assess its effects on eventual infarct size as measured by electrocardiographic, enzymatic, and scintigraphic criteria. Of the 71 patients with infarction, 35 received GL enzyme and 36 placebo within 6 h of the onset of chest pain. GL enzyme injected into a peripheral vein produced no adverse changes in the clinical, haemodynamic, biochemical, or haematological variables studied. GL enzyme reduced precordial electrocardiographic indices of infarct size as reflected by a diminution (p<0·02) in the degree of both R wave loss and Q wave development. In addition, the number of leads developing pathological Q waves (NΔQ≥2), a sign of progression from ischaemia to necrosis, was reduced (p<0·05) after GL nzyme treatment. However, there were no significant differences in infarct size as measured by cumulative creatine kinase MB isoenzyme release or technietium-99m pyrophosphate scintigraphic infarct area, or in clinical outcome during the hospital stay. Interpretation of the enzymatic and scintigraphic data was complicated by chance bias in pre-treatment randomisation which resulted in more (p<0·05) patients with severe haemodynamic impairment (and hence probably larger infarct sizes) entering the GL enzyme group. Nonetheless, a favourable effect of GL enzyme on infarct size was demonstrated by precordial electrocardiographic QRS mapping, where each patient acts as his or her own control.

Infarct sizing with technetium-99m stannous pyrophosphate scintigraphy in dogs and man; relationship between scintigraphic and praecordial mapping estimates of infarct size in patients.

The present study was performed in order to evaluate the ability of technetium-99m stannous pyrophosphate (99mTc-PYP) myocardial scintigrams to size infarcts in experimental animals and man. In 10 dogs with proximal left anterior descending coronary artery occlusion and acute anterior myocardial infarcts, there was a significant correlation between scintigraphic infarct size and histological infarct weight (P less than 0.01). In 25 patients with acute anterior or anterolateral myocardial infarcts, there was a significant correlation between relatively large infarct size determined scintigraphically and the acute development of left ventricular failure. There was some overlap, however, in 99mTc-PYP scintigraphic infarct size between patients who did and did not develop left ventricular failure with infarction. Presumably this is explained by some patients having had earlier myocardial damage and thus developing left ventricular failure with relatively small new infarcts. There was also a statistically significant, but weak, correlation in patients between scintigraphic infarct size and precordial ST segment mapping including peak ST segment elevation (P less than 0.05) and the number of praecordial sites with ST segment elevation equal to or greater than 2 mm (P less than 0.01). The data suggest that 99mTc-PYP scintigrams and praecordial mapping measure some similar but some dissimilar aspects of infarct size in patients, and that 99mTc-PYP scintigraphy does size acute anterior and anterolateral infarcts in experimental animals and patients.

Experimental myocardial infarction. III. Recovery of left ventricular function in the healing phase. Contribution of increased fiber shortening in noninfarcted myocardium

In the presence of focal myocardial damage, stroke volume may be maintained by ventricular dilatation, resulting in an increased left ventricular end-diastolic volume, or by increased fiber shortening in noninfarcted muscle. Relative contribution of these factors was examined in 5 shamoperated and 10 coronary-ligated dogs studied 4 to 7 days after surgery. Utilizing spherical formulas, stroke volume (SV), end-diastolic volume (EDV), and infarct size (IS) as a fraction of the weight of the left ventricle were measured in vivo or at postmortem, and the fiber-shortening fraction (FSF) in noninfarcted muscle was calculated: FSF = [l − 3 1 − ( SV EDV ] (1 − IS) When left ventricular end-diastolic pressure was kept in the range of 5 to 10 mm. Hg, stroke volume was well maintained in dogs with small (infarct size less than 20 per cent of the left ventricle) and large (infarct size greater than 20 per cent of the left ventricle) infarcts, and did not differ from shams. However, calculation of the fiber-shortening fraction gave values of 0.17 ± 0.03 (S.E.M.) for shams, 0.22 ± 0.01 for the 5 animals with small infarcts, and 0.36 ± 0.07 for the 5 animals with large infarcts, indicating increased shortening in noninfarcted muscle. Left ventricular enddiastolic volume was not increased; on the contrary, the values were 36 ± 5 ml. per 100 Gm. of left ventricle for animals with small infarcts, and 35 ± 4 ml. per 100 Gm. of left ventricle for animals with large infarcts, compared with 51 ± 2 ml. per 100 Gm. of left ventricle for shams, suggesting that compliance is reduced in infarcted muscle. This study shows that hemodynamic compensation in acute myocardial infarction may occur by increased shortening of nonifarcted muscle.